During the last year, I have used CGL facilities for many pharmacokinetic, pharmacodynamic, diffusion, and optimal control simulations. We are currently involved in three major areas of research: 1) Optimal control theory applied to dosing drugs that exhibit tolerance, 2) the diffusion of chemical entities through porous membranes (polymeric and biological), and 3) the mapping of the cGMP tolerance kinetics (both development and recovery) in response to glycerol trinitrate (nitroglycerin or GTN). In previous years, we selected different pharmacokinetic/pharmacodynamic (PK/PD) models for tolerance and simulated these models at the Computer Graphics Laboratory. The optimal surfaces describing an optimal dosing regimen for some given objective function can best be described by 2-D and 3-D plots. This work was done using the interactive graphics workstations in CGL. This year we added another mathematical model to the array of tolerance models. This model is still being developed and is based upon experimental work with LLC-PK1 cells and GTN. We have obtained some experimental results regarding the kinetic development of tolerance in this cell line. We are actively mathematically modeling this kinetic process and are doing simulations too. We hope to do similar simulations and optimal control calculations on CGL resources. We will continue to modify our diffusion models as well as the boundary conditions for these problems. We would like to set up a computer program, possibly using the MidasPlus delegate facility, that would graphically show different chemical entities diffusing through porous membranes (via Brownian motion, and even electro-osmotic flow) and possibly relate thermodynamic characteristics (partition coefficientss, etc.) to the diffusion of these chemicals through different types of membranes.